rs755309239

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080399.3(OC90):​c.1271C>T​(p.Ala424Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

OC90
NM_001080399.3 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320
Variant links:
Genes affected
OC90 (HGNC:8100): (otoconin 90) Predicted to enable calcium ion binding activity and structural molecule activity. Predicted to be involved in otolith mineralization. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09434065).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OC90NM_001080399.3 linkc.1271C>T p.Ala424Val missense_variant Exon 14 of 14 ENST00000254627.4 NP_001073868.2 Q02509-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OC90ENST00000254627.4 linkc.1271C>T p.Ala424Val missense_variant Exon 14 of 14 2 NM_001080399.3 ENSP00000254627.3 Q02509-1
ENSG00000258417ENST00000262283.5 linkc.1907C>T p.Ala636Val missense_variant Exon 18 of 18 5 ENSP00000262283.5 I6L893

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.78
DANN
Benign
0.97
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.33
T;T
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.094
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.018
Sift
Benign
0.16
T;D
Sift4G
Benign
0.077
T;T
Vest4
0.12
MVP
0.048
MPC
0.0032
ClinPred
0.054
T
GERP RS
0.17
Varity_R
0.030
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755309239; hg19: chr8-133036891; API